Ductal variant prostate carcinoma is associated with a significantly shorter metastasis-free survival

Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the charact...

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Published in:European journal of cancer (1990) Vol. 148; pp. 440 - 450
Main Authors: Chow, Ken, Bedő, Justin, Ryan, Andrew, Agarwal, Dinesh, Bolton, Damien, Chan, Yee, Dundee, Philip, Frydenberg, Mark, Furrer, Marc A., Goad, Jeremy, Gyomber, Dennis, Hanegbi, Uri, Harewood, Laurence, King, Dennis, Lamb, Alastair D., Lawrentschuk, Nathan, Liodakis, Peter, Moon, Daniel, Murphy, Declan G., Peters, Justin S., Ruljancich, Paul, Verrill, Clare L., Webb, David, Wong, Lih-Ming, Zargar, Homayoun, Costello, Anthony J., Papenfuss, Anthony T., Hovens, Christopher M., Corcoran, Niall M.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01.05.2021
Elsevier Science Ltd
Subjects:
Adenocarcinoma
Adenocarcinoma - mortality
Adenocarcinoma - secondary
Adenocarcinoma - surgery
Aged
Cancer surgery
Carcinoma, Ductal - mortality
Carcinoma, Ductal - secondary
Carcinoma, Ductal - surgery
Cell division
Copy number
Ductal adenocarcinoma
Follow-Up Studies
Histology
Humans
Male
Matching
Metastases
Metastasis
Metastasis-free survival
Middle Aged
Patients
Prognosis
Prospective Studies
Prostate
Prostate cancer
Prostate carcinoma
Prostatectomy
Prostatectomy - mortality
Prostatic Neoplasms - mortality
Prostatic Neoplasms - pathology
Prostatic Neoplasms - surgery
Retrospective Studies
Survival
Survival analysis
Survival Rate
Treatment resistance
Urological surgery
Ductal adenocarcinoma
Prostate cancer
Metastasis-free survival
ISSN:0959-8049, 1879-0852, 1879-0852
Online Access:Get full text
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Summary:Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the characteristics of ductal adenocarcinoma, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival. Patients with ductal variant histology from two institutional databases who underwent radical prostatectomies were identified and compared with an independent acinar adenocarcinoma cohort. After propensity score matching, the effect of the presence of ductal adenocarcinoma on time to biochemical recurrence, initiation of salvage therapy and the development of metastatic disease was determined. Deep whole-exome sequencing was performed for selected cases (n = 8). A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 versus 22.0 months, p = 0.03) and metastasis-free survival (6.7 versus 78.6 months, p < 0.0001). Ductal variant histology was consistently associated with RB1 loss, as well as copy number gains in TAP1, SLC4A2 and EHHADH. The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to initiation of salvage therapies and the onset of metastatic disease. These features appear to be driven by uncoupling of chromosomal duplication from cell division, resulting in widespread copy number aberration with specific gain of genes implicated in treatment resistance. •Ductal adenocarcinoma of the prostate is more clinically aggressive than acinar adenocarcinoma.•Ductal adenocarcinoma has shorter time to metastasis.•This is the first large non-registry–based study to use metastasis-free survival as an end-point.•RB1 loss may be a key molecular driver in clinical difference.
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ISSN:0959-8049
1879-0852
1879-0852
DOI:10.1016/j.ejca.2020.12.030